Evidence map›Paper›PMID 41131620›Full record

ArticleGenome biology2025

Identification of microprotein-coding intronic polyadenylation isoforms and function in genotoxic anticancer drug response.

Alexandre Devaux, Iris Tanaka, Quentin Fouilleul, Amélie Heneman-Masurel, Mandy Cadix, Sophie Michallet, Alina Chakraborty, Céline M Labbé, Nicolas Fontrodona, Subhadarsini Sahoo and 13 more

Abstract read
In one paragraph

Article in Genome biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Alexandre Devaux *INSERM U1278, CNRS UMR3348, Institut Curie, Université PSL, Orsay, 91400, France.
Iris Tanaka *INSERM U1278, CNRS UMR3348, Institut Curie, Université PSL, Orsay, 91400, France.
Quentin FouilleulINSERM U1278, CNRS UMR3348, Institut Curie, Université PSL, Orsay, 91400, France.
Amélie Heneman-MasurelINSERM U1278, CNRS UMR3348, Institut Curie, Université PSL, Orsay, 91400, France.
Mandy CadixINSERM U1278, CNRS UMR3348, Institut Curie, Université PSL, Orsay, 91400, France.
Sophie MichalletINSERM U1209, CNRS UMR5309, Team RNA Splicing, Cell Signaling and Response to Therapies, Institute For Advanced Biosciences, University Grenoble Alpes, Grenoble, 38000, France.
Alina ChakrabortyINSERM U1278, CNRS UMR3348, Institut Curie, Université PSL, Orsay, 91400, France.
Céline M LabbéINSERM U1278, CNRS UMR3348, Institut Curie, Université PSL, Orsay, 91400, France.
Nicolas FontrodonaCNRS UMR 5239, Ecole Normale Supérieure de Lyon, Lyon, 69007, France.
Subhadarsini SahooINSERM U1278, CNRS UMR3348, Institut Curie, Université PSL, Orsay, 91400, France.
Jean-Baptiste ClaudeCNRS UMR 5239, Ecole Normale Supérieure de Lyon, Lyon, 69007, France.
Marc DelogerINSERM U900, Mines Paris Tech, Institut Curie, Paris, 75000, France.
Pierre GestraudINSERM U900, Mines Paris Tech, Institut Curie, Paris, 75000, France.
Ludovic TessierINSERM U1278, CNRS UMR3348, Institut Curie, Université PSL, Orsay, 91400, France.
Hussein MortadaCNRS UMR 5239, Ecole Normale Supérieure de Lyon, Lyon, 69007, France.
Sonia LameirasInstitut Curie, ICGex NGS Platform, Paris, 75000, France.
Virginie RaynalInstitut Curie, ICGex NGS Platform, Paris, 75000, France.
Sylvain BaulandeInstitut Curie, ICGex NGS Platform, Paris, 75000, France.
Nicolas ServantINSERM U900, Mines Paris Tech, Institut Curie, Paris, 75000, France.
Didier AuboeufCNRS UMR 5239, Ecole Normale Supérieure de Lyon, Lyon, 69007, France.
Béatrice EyminINSERM U1209, CNRS UMR5309, Team RNA Splicing, Cell Signaling and Response to Therapies, Institute For Advanced Biosciences, University Grenoble Alpes, Grenoble, 38000, France.
Stéphan VagnerINSERM U1278, CNRS UMR3348, Institut Curie, Université PSL, Orsay, 91400, France.
Martin DutertreINSERM U1278, CNRS UMR3348, Institut Curie, Université PSL, Orsay, 91400, France. martin.dutertre@curie.fr.

Funding

Fondation pour la Recherche Médicale DBI20141231314Institut Curie ICGexInstitut National Du Cancer 2015-141Ligue Contre le Cancer équipe labellisée
6 · The paper itself

Abstract

backgroundMany transcript isoforms generated by intronic polyadenylation (IPA) encode isoforms of canonical proteins. Microproteins are an emerging class of small proteins translated from small open reading frames (sORFs) in noncoding RNAs and mRNAs, but their production by IPA isoforms is unknown.

resultsHere, by crossing 3'-seq, Ribo-Seq, and mass-spectrometry data, we identify 297 genes with a microprotein-coding IPA isoform terminating in a 5'UTR intron (coined miP-5'UTR-IPA isoform). By 3'-seq and long-read RNA-seq analyses in lung cancer cells treated with cisplatin, a DNA-cross-linking anticancer drug, we find that cisplatin globally favors the expression of (miP-5'UTR-)IPA isoforms relative to full-length mRNAs, mainly by decreasing the latter through an inhibition of transcription processivity in a FANCD2 and senataxin-dependent manner. The cisplatin-regulated miP-5'UTR-IPA isoform in the PRKAR1B gene is translated, as it is associated with light polysome fractions and contains Ribo-Seq-supported sORFs in its alternative last exon, and the microprotein (PRKAR1B-IPA-miP2) encoded by its sORF#2 is detected by Western blot and immunofluorescence. CRISPR editing of either the IPA site or the sORF#2 initiation site leads to decreased cell growth inhibition by cisplatin and camptothecin, another genotoxic drug. Mechanistically, PRKAR1B-IPA-miP2 promotes p53 protein induction by cisplatin. Finally, 70 miP-5'UTR-IPA isoforms are detected in normal cells, and 143 are upregulated by cisplatin.

conclusionsHere, we show that IPA isoforms are a novel source of microproteins, and we reveal the novel paradigm of miP-5'UTR-IPA genes that produce both a canonical full-length mRNA and a microprotein-coding IPA isoform.

Indexed as

Antineoplastic AgentsIntronsPolyadenylation5' Untranslated RegionsCell Line, TumorCisplatinHumansOpen Reading FramesProtein IsoformsRNA, Messenger5' Untranslated RegionsAntineoplastic AgentsCisplatinProtein IsoformsRNA, MessengerAlternative last exonDNA-damaging agentIntronic polyadenylationMicropeptideSmall ORF

Identifiers

PMID41131620
PMCPMC12548281

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.